Abstract
Aim: We aim to explore the blood-based sex-differential DNA methylation profiles in patients with Alzheimer’s disease (AD). Methods: The same analytical pipeline and meta-analysis procedure were applied to 254 patients with AD and 261 matched healthy controls (HC) from four blood-based datasets to identify sex-differentially methylated positions (sex-DMPs) and their biological functions. We further reviewed brain-based sex-DMPs previously reported in AD and intersected with blood-based sex-DMPs. Results: We identified 134 sex-DMPs in AD, 88 were unique to AD, and 46 were shared with HC. Eleven novel sex-DMPs and 28 sex-DMPs consistent across blood and brain were recognized for the first time. Differentially methylated genes, such as COL25A1 , MSUT2 , ELAVL4 , SLC17A7 , EPHA4 , and PPP2CB , were closely related to the pathogenesis of AD. In addition, immune-related processes were enriched in the enrichment analysis. Conclusion: Sex-differential DNA methylation in blood provides potential biomarkers for AD pathogenesis, and also points to potential drug targets for precision medicine.
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